1. Field of the Invention
The present invention relates to an .alpha.-keto acid/amino acid salt compound and to a process for its production.
2. Description of the Background
Amino acid salts of .alpha.-keto acids are known to be effective for the treatment of patients afflicated with renal disorders caused by uremia, and the like, and with hepatic disorders caused by hyperammoniemia, and the like. The salts are obtained in crystalline form and anhydrous crystals or crystals containing a very small amount of water have been prepared (Japanese Patent Publication Nos. 58-38421 and 60-24094).
U.S. Pat. Nos. 4,320,146; 4,228,099; 4,296,127 and 4,352,814 disclose pharmaceutically useful anhydrous, as well as hydrated amino acid salts of .alpha.-keto acids. These salts are formed from the likes of such amino acids as arginine, ornithine, histidine, lysine and threonine. The salts can be represented by the formula: AN.multidot..chi.H.sub.2 O, wherein A represents an amino acid, N represents an .alpha.-keto acid and .chi. ranges from 0 to 1.
Amino acid salts of .alpha.-keto acids are very highly soluble in water to the extent of 50 to 70 wt. %. Accordingly, an advantage of this high solubility property is that the salts can be administered with a relatively small amount of water to a subject. However, difficulties in crystallization of the salt result in serious obstacles during production.
In the past crystals of the amino acid salts of .alpha.-keto acids have been obtained by freeze drying, crystallization from a solvent and the like. From the point of view of industrial production, solvent crystallization of the salt is preferred. However, when solvent crystallization is performed, it is extremely difficult to remove the solvent. In particular, since the amino acid salts of .alpha.-keto acids are used as drugs for treating patients having renal disorders or hepatic disorders, strict standards are required which place limits on the amount of residual solvent in the crystals. Thus very long times are required for drying the crystals. Furthermore, the amino acid salts of .alpha.-keto acids are sensitive to heat and are likely to color so that drying should be performed at a very low temperature in vacuum. Even under such conditions, the dissolution state of the salts deteriorates depending upon the particular salt. A need therefore continues to exist for an improved and simplified method of preparing the amino acid salts of .alpha.-keto acids.